It’s mid-May, when I hear from students who’ve used my human genetics textbook spring semester. Olivia Kegler, a senior at Cor Jesu Academy in St. Louis, e-mailed: “We’re wondering what you think the next major genetics project will be?”
The next e-mail, the table of contents for May’s American Journal of Human Genetics, answered Olivia’s question: whole exome sequencing.
The exome is the Cliff’s/Spark Notes version of the genome, the part that encodes the proteins that keep our bodies growing and going. It’s only about 2 percent of our 3.2 billion DNA bases, but it holds out hope for families with inherited diseases so rare that physicians are stymied, databases useless.
The May issue of AJHG has three interesting entries for exome sequencing: a combo of weak tooth enamel and overgrown gums (amelogenesis imperfecta and gingival hyperplasia syndrome), heart failure in babies (infantile mitochondrial cardiomyopathy), and a rapid-aging disease (hereditary progeroid syndrome).
For people with the same mysterious medical condition, whole exome sequencing looks for unusual DNA sequences that they share, often a single DNA base. If the implicated gene makes sense, the next step is to see if it's expressed – makes its protein – in the affected tissues. For the first case, the gene does its thing in the teeth and gums; for the second case, a mutation disrupts how chromosomes touch the inner surface of the nucleus, just like in the better-studied progeria that makes children look elderly; for the third case, the mutation shuts down mitochondrial energy factories in cardiac muscle, starving the hearts of babies. Whole exome sequencing makes sense, and can provide clues to treatments.
The media have begun to cover some of the first families to have whole exome sequencing. I’m following a family with two little girls who have visual loss and other symptoms. After spending thousands of dollars on tests that rounded up the usual suspects, with no answers, the parents sent the family’s DNA to a researcher who is sequencing their exomes.
Stay tuned … while celebrities have their genomes done and regular people have fun with DNA testing, for families with rare diseases, whole exome sequencing is finally bringing answers.